Scientists at The Wistar Institute described a novel mechanism through which astrocytes, the most abundant supporting cells in the brain, also promote cancer cell growth and metastasis in the brain.

According to a study published online in the journal Cancer Discovery, astrocytes provide fatty acids that activate the PPAR-gamma pathway in cancer cells, enhancing their proliferation.

Brain metastasis remains an important contributor to overall cancer mortality in patients with advanced-stage disease, especially lung, breast, colon and kidney carcinoma, and melanoma. Current therapeutic strategies have shown limited efficacy, underscoring the need to expand our knowledge of brain metastasis mechanisms to identify novel therapeutic targets.

“We know that cancer cells take advantage of the interaction with local cells, especially astrocytes, to survive and proliferate in the brain environment,” said Qing Chen, M.D., Ph.D., assistant professor in the Immunology, Microenvironment & Metastasis Program and senior author of the study. “We wanted to understand the nature of this interaction and what exactly astrocytes provide to support metastatic growth.”

Chen and her collaborators focused on clinically relevant mouse models of melanoma brain metastasis and showed that astrocytes promoted cancer cell proliferation. By investigating the molecular mechanisms of this interaction, they found that the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) pathway is activated in cancer cells that possess elevated ability to form brain metastasis, and it is even more active when these cells are co-cultured with astrocytes.

Genetic and pharmacologic blockade of PPAR-gamma signaling resulted in decreased cancer cell growth and a reduced response to astrocyte-induced proliferative effect, establishing the functional relevance of this pathway in brain metastasis.

Source: Science Daily